title: Interaction of Pseudomonas aeruginosa Exotoxin A with the human Sec61 complex suppresses passive calcium efflux from the endoplasmic reticulum.
abstract: According to live-cell calcium-imaging experiments, the Sec61 complex is a passive calcium-leak channel in the human endoplasmic reticulum (ER) membrane that is regulated by ER luminal immunoglobulin heavy chain binding protein (BiP) and cytosolic Ca(2+)-calmodulin. In single channel measurements, the open Sec61 complex is Ca(2+) permeable. It can be closed not only by interaction with BiP or Ca(2+)-calmodulin, but also with Pseudomonas aeruginosa Exotoxin A which can enter human cells by retrograde transport. Exotoxin A has been shown to interact with the Sec61 complex and, thereby, inhibit ER export of immunogenic peptides into the cytosol. Here, we show that Exotoxin A also inhibits passive Ca(2+) leakage from the ER in human cells, and we characterized the N-terminus of the Sec61 α-subunit as the relevant binding site for Exotoxin A.
authors.affiliation: Medical Biochemistry and Molecular Biology; Saarland University; Homburg, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Schäuble
authors.affiliation: Experimental and Clinical Pharmacology and Toxicology; Saarland University; Homburg, Germany.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Cavalié
authors.affiliation: Medical Biochemistry and Molecular Biology; Saarland University; Homburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Medical Biochemistry and Molecular Biology; Saarland University; Homburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005098:Exotoxins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D000069816:SEC Translocation Channels; D037521:Virulence Factors / Q000378:metabolism*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002118:Calcium; D005098:Exotoxins; D008565:Membrane Proteins; D009842:Oligopeptides; D000069816:SEC Translocation Channels; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C000613244:SEC61A1 protein, human
keywords: ER calcium leakage; Pseudomonas aeruginosa Exotoxin A; Sec61 complex; calcium homeostasis; endoplasmic reticulum